Effect of ATP-Sensitive Potassium Channel Inhibition on Coronary Metabolic Vasodilation in Humans

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 24; no. 5; pp. 905 - 910
• Main Authors: Farouque, H.M Omar, Worthley, Stephen G, Meredith, Ian T
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.05.2004; Hagerstown, MD Lippincott
• Subjects: Adenosine Triphosphate - physiology; Aged; Angioplasty, Balloon, Coronary; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiac Catheterization; Cardiac Pacing, Artificial; Cardiology. Vascular system; Coronary Angiography; Coronary Artery Disease - metabolism; Coronary Artery Disease - therapy; Coronary Circulation - drug effects; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Glyburide - pharmacology; Humans; Hyperemia - metabolism; Ion Transport - drug effects; Laser-Doppler Flowmetry; Male; Medical sciences; Middle Aged; Myocardium - metabolism; Potassium - metabolism; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels - physiology; Receptors, Drug - drug effects; Receptors, Drug - physiology; Reproducibility of Results; Vasodilation - drug effects; Human; sulfonylurea; Vasoconstriction; Cardiovascular disease; Vasodilation; ion channels; Blood flow; Vascular disease; coronary circulation; Vasomotricity; Atherosclerosis; Sulfonylureas; Hemodynamics; ATP; Potassium
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000125701.18648.48

OBJECTIVE—Experimental evidence indicates that ATP-sensitive potassium (KATP) channels regulate coronary blood flow (CBF). However, their contribution to human coronary metabolic vasodilation is unknown. METHODS AND RESULTS—Seventeen patients (12 male, age 58±10 years) were studied. Coronary hemodynamics were assessed before and after KATP channel inhibition with subselective intracoronary glibenclamide infused at 40 μg/min in an angiographically smooth coronary artery after successful percutaneous coronary intervention to another vessel. Metabolic vasodilation was induced by 2 minutes of rapid right ventricular pacing. Coronary blood velocity was measured with a Doppler guidewire and CBF calculated. The time course of hyperemia was recorded for 2 minutes after pacing, and hyperemic volume was estimated from the area under the flow-versus-time curve (AUC). Compared with vehicle infusion (0.9% saline), glibenclamide reduced resting CBF by 9% (P= 0.04) and increased resting coronary vascular resistance (CVR) by 15% (P= 0.03). Glibenclamide reduced pacing-induced peak CBF (50.8±6.8 versus 42.0±5.4 mL/min, P= 0.001), peak CBF corrected for baseline flow (25.1±4.6 versus 17.6±3.1 mL/min, P= 0.01), and increased minimum CVR (2.6±0.3 versus 3.1±0.3 mm Hg/mL per minute, P= 0.002). Compared with vehicle, glibenclamide reduced total AUC at 2 minutes (3535±397 versus 3027±326 mL, P= 0.001). CONCLUSIONS—Vascular KATP channels appear to be involved in functional coronary hyperemia after metabolic stimulation.